Prebiotics‐Encapsulated Probiotic Spores Regulate Gut Microbiota and Suppress Colon Cancer

Abstract While microbial‐based therapy has been considered as an effective strategy for treating diseases such as colon cancer, its safety remains the biggest challenge. Here, probiotics and prebiotics, which possess ideal biocompatibility and are extensively used as additives in food and pharmaceutical products, are combined to construct a safe microbiota‐modulating material. Through the host–guest chemistry between commercial Clostridium butyricum and chemically modified prebiotic dextran, prebiotics‐encapsulated probiotic spores (spores‐dex) are prepared. It is found that spores‐dex can specifically enrich in colon cancers after oral administration. In the lesion, dextran is fermented by C. butyricum , and thereby produces anti‐cancer short‐chain fatty acids (SCFAs). Additionally, spores‐dex regulate the gut microbiota, augment the abundance of SCFA‐producing bacteria (e.g., Eubacterium and Roseburia ), and markedly increase the overall richness of microbiota. In subcutaneous and orthotopic tumor models, drug‐loaded spores‐dex inhibit tumor growth up to 89% and 65%, respectively. Importantly, no obvious adverse effect is found. The work sheds light on the possibility of using a highly safe strategy to regulate gut microbiota, and provides a promising avenue for treating various gastrointestinal diseases.